The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform

David L Glanzman - One of the best experts on this subject based on the ideXlab platform.

  • Postsynaptic regulation of the development and long term plasticity of aplysia sensorimotor synapses in Cell culture
    Journal of Neurobiology, 1994
    Co-Authors: David L Glanzman
    Abstract:

    The monosynaptic component of the neuronal circuit that mediates the withdrawal reflex of Aplysia californica can be reconstituted in dissociated Cell culture. Study of these in vitro monosynaptic connections has yielded insights into the basic Cellular mechanisms of synaptogenesis and long-term synaptic plasticity. One such insight has been that the development of the presynaptic sensory neurons is strongly regulated by the Postsynaptic motor neuron. Sensory neurons which have been cocultured with a target motor neuron have more elaborate structures—characterized by neurites with more branches and varicosities—than do sensory neurons grown alone in culture or sensory neurons that have been cocultured with an inappropriate target Cell. Another way in which the motor neuron regulates the development of sensory neurons is apparent when sensorimotor cocultures with two presynaptic Cells are examined. In such cocultures the outgrowth from the different presynaptic Cells is obviously segregated on the processes of the Postsynaptic Cell. By contrast, when two sensory neurons are placed into Cell culture without a motor neuron, thier processes readily grow together. In addition to regulating the in vitro development of sensory neurons, the motor neuron also regulates learning-related changes in the structure of sensory neurons. Application of the endogenous facilitatory trasmitter serotonin (5-HT) causes long-term facilitation of in vitro sensorimotor synapses due in part to growth of new presynatpic varicosities. But 5-HT applied to sensory neurons alone in cultuer does not produce structural changes in these Cells. More recently it has been found that sensorimotor synapses in Cell culture can exhibit long-term potentiation (LTP). Like LTP of some hippocampal synapses, LTP of in vitro Aplysia syanpses is regulated by the voltage of the Postsynaptic Cell. Pairing high-frequency stimulation of sensory neurons with strong hyperpolarization of the motor neuron blocks the induction of LTP. Moreover, LTP of sensorimotor synapses can be induced in Hebbian fashion by pairing weak presynaptic stimulation with strong Postsynaptic depolarization. These findings implicate a Habbian mechanism in classical conditioning in Aplysia. They also indicate that Hebbian LTP is a phylogenetically ancient form of synaptic plasticity. 1994 John Wiley & Sons, Inc.

  • long term potentiation of aplysia sensorimotor synapses in Cell culture regulation by Postsynaptic voltage
    Proceedings of The Royal Society B: Biological Sciences, 1994
    Co-Authors: David L Glanzman
    Abstract:

    Long-term potentiation (LTP) has been proposed as a Cellular mechanism for associative learning in vertebrates. Induction of one type of LTP - observed at synapses in the CA1 region of the mammalian hippocampus - is regulated by the voltage of the Postsynaptic Cell. To date, a similar form of LTP has not been demonstrated for any invertebrate synapse. We now report that high-frequency stimulation can induce LTP of sensorimotor synapses of the marine mollusc Aplysia in Cell culture. Moreover, induction of this form of LTP appears to involve a voltage-dependent Postsynaptic mechanism because pairing tetanic stimulation of the presynaptic Cell with strong hyperpolarization of the Postsynaptic Cell blocks the induction of LTP.

Leonardo Guzman - One of the best experts on this subject based on the ideXlab platform.

  • Rational Design and In Vitro Evaluation of Novel Peptides Binding to Neuroligin-1 for Synaptic Targeting.
    Journal of Chemical Information and Modeling, 2020
    Co-Authors: Pilar Vásquez, Felipe Vidal, Josefa Torres, Verónica A. Jiménez, Leonardo Guzman
    Abstract:

    Neuroligin-1 (NL1) is a Postsynaptic Cell adhesion protein that plays a crucial role in synapsis and signaling between neurons. Due to its clustered distribution in synaptic clefts, NL1 appears as a novel potential site for synaptic targeting purposes. In this work, in silico protein topography analysis was employed to identify two prospective binding sites on the NL1 dimer surface in the 2:2 synaptic adhesion complex with β-neurexin (PDB code 3B3Q). Receptor-based rational design, Cell-penetrating capability prediction, molecular docking, molecular dynamics simulations, and binding free energy calculations were used to identify five heptapeptides candidates with favorable predicted profiles as non Cell-penetrating NL1-binding agents. Preliminary in vitro colocalization assays with NL1-transfected HEK 293 Cells confirmed that peptides remain in the extraCellular space without inducing detectable changes in Cell morphology. The highest NL1-colocatization capability was attained by the peptide ADEAIVA, whic...

  • rational design and in vitro evaluation of novel peptides binding to neuroligin 1 for synaptic targeting
    Journal of Chemical Information and Modeling, 2020
    Co-Authors: Pilar Vásquez, Felipe Vidal, Josefa Torres, Verónica A. Jiménez, Leonardo Guzman
    Abstract:

    Neuroligin-1 (NL1) is a Postsynaptic Cell adhesion protein that plays a crucial role in synapsis and signaling between neurons. Due to its clustered distribution in synaptic clefts, NL1 appears as a novel potential site for synaptic targeting purposes. In this work, in silico protein topography analysis was employed to identify two prospective binding sites on the NL1 dimer surface in the 2:2 synaptic adhesion complex with beta-neurexin (PDB code 3B3Q ). Receptor-based rational design, Cell-penetrating capability prediction, molecular docking, molecular dynamics simulations, and binding free energy calculations were used to identify five heptapeptides candidates with favorable predicted profiles as non Cell-penetrating NL1-binding agents. Preliminary in vitro colocalization assays with NL1-transfected HEK 293 Cells confirmed that peptides remain in the extraCellular space without inducing detectable changes in Cell morphology. The highest NL1-colocatization capability was attained by the peptide ADEAIVA, which appears as a promising candidate for the future development of specific NL1-targeting systems as part of synapse-directed therapies against central nervous system diseases.

Gyorgy Buzsaki - One of the best experts on this subject based on the ideXlab platform.

  • pyramidal Cell interneuron circuit architecture and dynamics in hippocampal networks
    Neuron, 2017
    Co-Authors: Daniel F English, Sam Mckenzie, Talfan Evans, Euisik Yoon, Gyorgy Buzsaki
    Abstract:

    Summary Excitatory control of inhibitory neurons is poorly understood due to the difficulty of studying synaptic connectivity in vivo . We inferred such connectivity through analysis of spike timing and validated this inference using juxtaCellular and optogenetic control of presynaptic spikes in behaving mice. We observed that neighboring CA1 neurons had stronger connections and that superficial pyramidal Cells projected more to deep interneurons. Connection probability and strength were skewed, with a minority of highly connected hubs. Divergent presynaptic connections led to synchrony between interneurons. Synchrony of convergent presynaptic inputs boosted Postsynaptic drive. Presynaptic firing frequency was read out by Postsynaptic neurons through short-term depression and facilitation, with individual pyramidal Cells and interneurons displaying a diversity of spike transmission filters. Additionally, spike transmission was strongly modulated by prior spike timing of the Postsynaptic Cell. These results bridge anatomical structure with physiological function.

Jeff W Lichtman - One of the best experts on this subject based on the ideXlab platform.

  • Reversing the Outcome of Synapse Elimination at Developing Neuromuscular Junctions In Vivo: Evidence for Synaptic Competition and Its Mechanism
    PLOS Biology, 2012
    Co-Authors: Stephen G. Turney, Jeff W Lichtman
    Abstract:

    During mammalian development, neuromuscular junctions and some other Postsynaptic Cells transition from multiple- to single-innervation as synaptic sites are exchanged between different axons. It is unclear whether one axon invades synaptic sites to drive off other inputs or alternatively axons expand their territory in response to sites vacated by other axons. Here we show that soon-to-be-eliminated axons rapidly reverse fate and grow to occupy vacant sites at a neuromuscular junction after laser removal of a stronger input. This reversal supports the idea that axons take over sites that were previously vacated. Indeed, during normal development we observed withdrawal followed by takeover. The stimulus for axon growth is not Postsynaptic Cell inactivity because axons grow into unoccupied sites even when target Cells are functionally innervated. These results demonstrate competition at the synaptic level and enable us to provide a conceptual framework for understanding this form of synaptic plasticity.

  • Asynchronous Synapse Elimination in Neonatal Motor Units
    Neuron, 2001
    Co-Authors: Cynthia R Keller-peck, Mark K Walsh, Wen Biao Gan, Guoping Feng, Joshua R Sanes, Jeff W Lichtman
    Abstract:

    In developing muscle, synapse elimination reduces the number of motor axons that innervate each Postsynaptic Cell. This loss of connections is thought to be a consequence of axon branch trimming. However, branch retraction has not been observed directly, and ...\n

  • Interactions between nerve and muscle: synapse elimination at the developing neuromuscular junction.
    Developmental Biology, 1993
    Co-Authors: Howard Colman, Jeff W Lichtman
    Abstract:

    Studies of synaptogenesis at the developing neuromuscular junction have provided a wealth of information regarding the various mechanisms that are involved in the formation of synaptic connections. In addition to synapse formation, however, the mature pattern of innervation at the neuromuscular junction (and elsewhere in the nervous system) depends on a significant loss of synaptic connections during development. The molecular mechanisms involved in the process of synapse elimination are not understood. Recent work at the neuromuscular junction suggests that changes in the Postsynaptic Cell may be necessary in order for nerve terminals to be eliminated. Thus, in contrast to synapse formation in which an axon terminal initiates a cascade of changes leading to the formation of pre- and Postsynaptic specializations, synapse elimination may be initiated by local changes in the Postsynaptic Cell that disassemble the Postsynaptic apparatus and ultimately remove the overlying terminal. In this review, we wish to examine the potential role that some of the factors involved in synapse formation might play in the less-well-understood phenomenon of synapse elimination.

Tomoyuki Yoshida - One of the best experts on this subject based on the ideXlab platform.

  • in situ screening for Postsynaptic Cell adhesion molecules during synapse formation
    Journal of Biochemistry, 2017
    Co-Authors: Takeshi Uemura, Tomoko Shiroshima, Asami Maeda, Misato Yasumura, Takashi Shimada, Yuko Fukata, Masaki Fukata, Tomoyuki Yoshida
    Abstract:

    : Neuronal synapse formation is regulated by pre- and Postsynaptic Cell adhesion molecules. Presynaptic neurexins (NRXNs) and receptor protein tyrosine phosphatases (RPTPs; PTPδ, PTPσ and LAR in mammals) can induce Postsynaptic differentiation through the interaction with various Postsynaptic Cell adhesion molecules. Here, we developed a novel in situ screening method to identify Postsynaptic membranous proteins involved in synaptogenesis. Magnetic beads coated with the extraCellular domains of NRXN1β(-S4) and PTPδ-A6 variants preferentially induced excitatory Postsynaptic differentiation on the beads' surface when co-cultured with cortical neurons. After inducing Postsynaptic sites on these beads, protein complexes including NRXN1β(-S4)/PTPδ-A6 and their ligands on the neuronal membrane were chemically cross-linked and purified using a magnetic separator. Liquid chromatography-tandem mass spectrometry analysis of the complexes revealed two types of Postsynaptic ligands for NRXN1β(-S4) and PTPδ-A6, one has an activity to induce presynaptic differentiation in a trans manner, whereas the other has no such activity. These results suggest that synapse formation is regulated by the interplay between presynaptic NRXN/PTPδ and their Postsynaptic ligands with functionally different impacts on pre- and Postsynaptic differentiation. Thus, our in situ screening method for identifying synapse-organizing complexes will help to understand the molecular basis for elaborate neuronal networks.